Embryonal rhabdomyosarcoma

by Jason Wasserman MD PhD FRCPC
July 23, 2024

Background:

Embryonal rhabdomyosarcoma (ERMS) is a malignant (cancerous) soft tissue tumour that arises from immature skeletal muscle cells. It is the most common type of rhabdomyosarcoma, accounting for about 60-70% of all cases. This type of cancer predominantly affects children, typically those under the age of 10. Embryonal rhabdomyosarcoma commonly occurs in the head and neck region, genitourinary tract, and, less frequently, in the extremities and trunk.

What are the symptoms of embryonal rhabdomyosarcoma?

The symptoms of embryonal rhabdomyosarcoma vary depending on the tumour’s location. Common symptoms include:

1. Head and neck region: A visible or palpable mass, nasal congestion, bleeding, swallowing difficulties, and bulging of the eye.
2. Genitourinary tract: Difficulty urinating, blood in the urine, a palpable mass in the abdomen, and in girls, a mass that protrudes from the vagina.
3. Extremities and trunk: A lump or swelling, pain, and limited range of motion.

Other general symptoms can include fatigue, weight loss, and fever if the cancer has spread.

What causes of embryonal rhabdomyosarcoma?

The exact cause of embryonal rhabdomyosarcoma is not well understood, but several factors are thought to contribute to its development:

1. Genetic mutations: Abnormal gene changes that regulate cell growth and differentiation can lead to cancer. Specific genetic alterations, such as mutations in the TP53 gene or the presence of the PAX3-FKHR fusion gene, have been associated with rhabdomyosarcoma.
2. Inherited syndromes: Certain genetic syndromes, such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and Costello syndrome, increase the risk of developing embryonal rhabdomyosarcoma.
3. Environmental factors: Although not well-established, exposure to certain chemicals or radiation might play a role in developing soft tissue sarcomas, including embryonal rhabdomyosarcoma.

How is this diagnosis made?

The first diagnosis of embryonal rhabdomyosarcoma is usually made after a small tumour sample is removed in a procedure called a biopsy. The biopsy tissue is then sent to a pathologist, who examines it under a microscope. After a pathologist makes a diagnosis of embryonal rhabdomyosarcoma, patients are often treated first with chemotherapy and/or radiation therapy, followed by surgery. The tumour is then removed completely as a resection specimen and sent to pathology for examination.

Microscopic features of this tumour

When examined under the microscope, the tumour comprises immature muscle cells called rhabdomyoblasts. The nucleus (the part that holds the genetic material of the cell) is typically small, round, and hyperchromatic (dark blue). The nucleus may be eccentric (pushed to the side of the cell), and a small amount of pink cytoplasm (the material inside the cell’s body) may be seen beside it.

Immunohistochemistry

Immunohistochemistry is a special test that allows pathologists to look for specific types of proteins inside cells. Pathologists use the results of this test to determine the cell’s function and where in the body the cell came from. When immunohistochemistry is performed on embryonal rhabdomyosarcoma, the tumour cells are typically positive for muscle markers such as desmin, myogenin, and MyoD1.

Molecular tests

Molecular tests such as fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) may be performed to look for specific genetic changes. The primary reason for performing these types of tests on embryonal rhabdomyosarcoma is to help rule out other types of rhabdomyosarcoma that can look very similar when examined under the microscope. For example, alveolar rhabdomyosarcoma contains a genetic change involving the FOXO1 gene, but this change is not seen in embryonal rhabdomyosarcoma.

Grade

Pathologists use the French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading system to assign a grade to most types of soft tissue cancers. However, this system is not commonly applied to embryonal rhabdomyosarcoma.

Tumour size

Tumour size is important because tumours less than 5 cm are less likely to spread to other body parts and are associated with a better prognosis. Tumour size is also used to determine the pathologic tumour stage (pT).

Treatment effect

If you received chemotherapy and/or radiation therapy before the operation to remove the tumour, your pathologist will examine all the tissue sent to pathology to see how much of the tumour was still alive at the time it was removed from the body. Pathologists use the term viable to describe tissue that was still alive when it was removed from the body. In contrast, pathologists use the term non-viable to describe tissue that was not alive when it was removed from the body. Most commonly, your pathologist will describe the percentage of tumours that is non-viable.

Perineural invasion

Pathologists use the term “perineural invasion” to describe a situation where cancer cells attach to or invade a nerve. “Intraneural invasion” is a related term that specifically refers to cancer cells found inside a nerve. Nerves, resembling long wires, consist of groups of cells known as neurons. These nerves, present throughout the body, transmit information such as temperature, pressure, and pain between the body and the brain. The presence of perineural invasion is important because it allows cancer cells to travel along the nerve into nearby organs and tissues, raising the risk of the tumour recurring after surgery.

Lymphovascular invasion

Lymphovascular invasion occurs when cancer cells invade a blood vessel or lymphatic channel. Blood vessels, thin tubes that carry blood throughout the body, contrast with lymphatic channels, which carry a fluid called lymph instead of blood. These lymphatic channels connect to small immune organs known as lymph nodes scattered throughout the body. Lymphovascular invasion is important because it enables cancer cells to spread to other body parts, including lymph nodes or the lungs, via the blood or lymphatic vessels. As such, lymphovascular invasion is associated with an increased risk of developing metastatic disease.

Margins

In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure, like an excision or resection, that removes the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some cancer may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small lymphatic vessels. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body, such as a lymph node, is called a metastasis.

Cancer cells typically spread first to lymph nodes close to the tumour, although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist, and the results of this examination will be described in your report. The examination of lymph nodes is important for two reasons. First, this information determines the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment, such as chemotherapy, radiation therapy, or immunotherapy, is required.

Some helpful definitions:

• Positive: Positive means that cancer cells were found in the lymph node being examined.
• Negative: Negative means that no cancer cells were found in the lymph node being examined.
• Deposit: The term deposit describes a group of cancer cells inside a lymph node. Some reports include the size of the largest deposit. A similar term is “focus”.
• Extranodal extension: Extranodal extension means that the tumour cells have broken through the capsule on the outside of the lymph node and have spread into the surrounding tissue.

Pathologic stage (pTNM)

​The pathologic stage for embryonal rhabdomyosarcoma is based on the TNM staging system, an internationally recognized system created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means a more advanced disease and a worse prognosis.

Tumour stage (pT)

The tumour stage for embryonal rhabdomyosarcoma is based on the tumour size and the tumour extension into surrounding tissues. The staging system used also varies based on the body part involved. For example, a 5-centimetre tumour that starts in the head will be given a different tumour stage than a tumour that starts deep in the back of the abdomen (the retroperitoneum). However, in most body sites, the tumour stage includes the tumour size and whether the tumour has grown into surrounding body parts.

Head and neck

• T1 – The tumour is no greater than 2 centimetres in size.
• T2 – The tumour is between 2 and 4 centimetres in size.
• T3 – The tumour is greater than 4 centimetres in size.
• T4 – The tumour has grown into surrounding tissues such as the bones of the face or skull, the eye, the larger blood vessels in the neck, or the brain.

Chest, back, or stomach and the arms or legs (trunk and extremities)

• T1 – The tumour is no greater than 5 centimetres in size.
• T2 – The tumour is between 5 and 10 centimetres in size.
• T3 – The tumour is between 10 and 15 centimetres in size.
• T4 – The tumour is greater than 15 centimetres in size.

Abdomen and organs inside the chest (thoracic visceral organs)

• T1 – The tumour is only seen in one organ.
• T2 – The tumour has grown into the connective tissue surrounding the organ from which it started.
• T3 – The tumour has grown into at least one other organ.
• T4 – Multiple tumours are found.

Retroperitoneum (the space at the very back of the abdominal cavity)

• T1 – The tumour is no greater than 5 centimetres in size.
• T2 – The tumour is between 5 and 10 centimetres in size.
• T3 – The tumour is between 10 and 15 centimetres in size.
• T4 – The tumour is greater than 15 centimetres in size.

Tissue around the eye (orbit)

• T1 – The tumour is no greater than 2 centimetres in size.
• T2 – The tumour is greater than 2 centimetres in size but has not grown into the bones surrounding the eye.
• T3 – The tumour has grown into the bones surrounding the eye or other bones of the skull.
• T4 – The tumour has grown into the eye (the globe) or the surrounding tissues such as the eyelids, sinuses, or brain.

Nodal stage (pN)

Embryonal rhabdomyosarcoma is given a nodal stage of 0 or 1 based on the presence or absence of tumour cells in one or more lymph nodes. If no tumour cells are seen in any lymph nodes, the nodal stage is N0. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined, and the nodal stage is listed as NX.  If tumour cells are found in any lymph nodes, then the nodal stage is listed as N1.

About this article

Doctors wrote this article to help you read and understand your pathology report. If you have additional questions, contact us.

Other helpful resources

Atlas of Pathology